The screening of cellular pathways for new therapeutics can be advanced more rapidly if primary drug targets can be simultaneously counter-screened for secondary targets, such as for off-target action. Such duoplex measurements have been unavailable in a homogeneous, rapid assay format. Here we describe such capability using the Alpha SureFire® Ultra™ Multiplex detection system. Incorporating dual CaptSure™ technologies, these assays provide duoplexed measurements of virtually all AlphaLISA SureFire Ultra assay targets, where scientists can pick whichever two targets they require to measure on a particular day. Further, each well of an assay plate can measure any two phosphoprotein targets in the assay range. Such pick-and-pack capability and unsurpassed sensitivity provides a new dimension to cellular research and drug discovery efforts.